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Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji Yezhong Wang Yingjia Li Yongyi Ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li Faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi Zeng Chunyan Wang Li Yang Cheng Long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal university-Panyu Central hospital Joint Laboratory of Translational medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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Deciphering the molecular mechanisms of Simiaowan in the treatment of hyperuricemia: in vivo and in silico approaches

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Traditional Medicine Research 2025年第2期10卷 37-54页

作者： Yong-Chang Zeng Jun-Hong Wu Dan-Dan Xu Kang He Chang-Qing Liu Li-Fei Song Zheng-Zhi Wu Qian-Qian Jiang Shao-Yu Liang Department of Neurology The First Affiliated Hospital of Shenzhen UniversityShenzhen 518020China Pharmaceutical Department The Affiliated TCM Hospital of Guangzhou Medical UniversityGuangzhou 510000China School of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang 550025China guangzhou Zeli medical Technology Co. Ltd.Guangzhou 510700China

Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for ***,the bioactive components and underlying mechanisms have not been *** objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular ***:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of ***-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing *** pharmacology and molecular docking were utilized to elucidate the potential targets and underlying ***:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active *** 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling *** docking indicated that active compounds(***,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(*** carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:S

关键词： hyperuricemia network pharmacology serum pharmacochemistry Simiaowan UPLC-Q-Exactive-MS/MS

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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong Department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National medical Products Administration(NMPA)Key Laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Tumor inflammation-specific self-amplifying fluorescent molecular probes induce an anti-tumor immune response

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Science China Chemistry 2025年第1期 273-287页

作者： Shuguang Yang Lijun Hu Hong Xiao Zecong Xiao Xintao Shuai PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-sen University Department of Ultrasound The Fifth Affiliated Hospital Sun Yat-sen University Department of medical Ultrasound The Third Affiliated Hospital of Sun Yat-sen University Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat-sen University

Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTPICG, for photodynamic therapy(PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and ***, PDT efficiently incites immunogenic cell death(ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells(DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils(TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.

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Effects of lower body positive pressure treadmill on functional improvement in knee osteoarthritis:A randomized clinical trial study

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World Journal of Clinical Cases 2021年第34期9卷 10604-10615页

作者： Hong-Xin Chen Yao-Xuan Zhan Hai-Ning Ou Yao-Yao You Wan-Ying Li Shan-Shan Jiang Mei-Feng Zheng Lin-Zi Zhang Ke Chen Qiu-Xia Chen Department of Rehabilitation Medicine The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700Guangdong ProvinceChina Department of General Medicine The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700Guangdong ProvinceChina guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700Guangdong ProvinceChina Department of Rehabilitation Medicine Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Rehabilitation Medicine Guangdong Pharmaceutical UniversityGuangzhou 510006Guangdong ProvinceChina Department of Osteology The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700Guangdong ProvinceChina

BACKGROUND Knee joint pain and stiffness are the two main symptoms of knee osteoarthritis(OA)and thus restrict a patient’s activities,such as walking and walking up and *** lower body positive pressure(LBPP)treadmill as one of the emerging body weight support system devices brings new hope for exerciserelated rehabilitation for knee OA *** To investigate the biomechanical effects and the subjective clinical assessment of LBPP treadmill walking exercise when compared with conventional therapy in mild to moderate knee OA *** Eighteen patients with mild-to-moderate knee OA were recruited in this randomized controlled trial(RCT)*** eligible knee OA patients were randomly assigned to two groups:LBPP and control *** patients in the LBPP group performed an LBPP walking training program for 30 min/session per day,6 d per week for 2 wk whereas the patients in the control group performed walking on the ground for the same *** patients underwent clinical assessments and three-dimensional gait analysis at pre-and 2-wk *** The Western Ontario and McMaster Universities Arthritis Index and visual analog scale scores in both the LBPP group and control group were found to decrease significantly at the post-treatment point than the pre-treatment point(LBPP:70.25±13.93 vs 40.50±11.86;3.88±0.99 vs 1.63±0.52;control:69.20±8.88 vs 48.10±8.67;3.80±0.79 vs 2.60±0.70,P<0.001).Moreover,compared with the control group,the LBPP group showed more improvements in walking speed(P=0.007),stride length(P=0.037),and knee range of motion(P=0.048)during walking,which represented more improvement in walking *** The results of our RCT study showed that the LBPP group has a greater effect on improving gait parameters than the conventional group,although there was no significant advantage in clinical *** finding indicates that LBPP treadmill walking training might be an effective approach for alleviating pai

关键词： Lower body positive pressure Three-dimensional gait analysis Walking training Rehabilitation Knee osteoarthritis

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Primary intramedullary melanoma of lumbar spinal cord: A case report

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World Journal of Clinical Cases 2021年第10期9卷 2352-2356页

作者： Le-Dong Sun Xin Chu Li Xu Xiu-Zhen Fan Yi Qian Da-Ming Zuo Department of Dermatology The Fifth Affiliated HospitalSouthern Medical UniversityGuangzhou 510900Guangdong ProvinceChina The fifth affiliated hospital Southern Medical UniversityGuangzhou 510900Guangdong ProvinceChina Department of medical Laboratory Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

BACKGROUND Primary intramedullary melanoma is a very rare tumor,most frequently occurring in the cervical and thoracic spinal *** SUMMARY We present a rare case in which the primary intramedullary melanoma was located in the lumbar spine.A 56-year-old man complained of progressive intermittent pain in the lumbar *** magnetic resonance imaging showed a spinal intramedullary tumor between the L3 and S1 *** tumor was resected entirely,and the diagnosis of malignant melanoma was confirmed by *** Primary melanoma of the spinal cord,particularly intramedullary localization,has rarely been reported in the previous *** describe a primary malignant melanoma of the lumbar spinal cord and discuss the challenges associated with the diagnosis.

关键词： Intramedullary melanoma Spinal cord Lumbar Magnetic resonance imaging Histopathological examination Immunohistochemical staining Case report

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Changes in lumbosacral spinal nerve roots on diffusion tensor imaging in spinal stenosis

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Neural Regeneration Research 2015年第11期10卷 1860-1864页

作者： Zhong-jun Hou Yong Huang Zi-wen Fan Xin-chun Li Bing-yi Cao Department of Radiology the Second Affiliated Hospital of Guangzhou Medical University Department of Orthopedics the Second Affiliated Hospital of Guangzhou Medical University Department of Radiology the First Affiliated Hospital of Guangzhou Medical University

Lumbosacral degenerative disc disease is a common cause of lower back and leg pain. Conventional T1-weighted imaging（T1WI） and T2-weighted imaging（T2WI） scans are commonly used to image spinal cord degeneration. However, these modalities are unable to image the entire lumbosacral spinal nerve roots. Thus, in the present study, we assessed the potential of diffusion tensor imaging（DTI） for quantitative assessment of compressed lumbosacral spinal nerve roots. Subjects were 20 young healthy volunteers and 31 patients with lumbosacral stenosis. T2 WI showed that the residual dural sac area was less than two-thirds that of the corresponding normal area in patients from L3 to S1 stenosis. On T1 WI and T2 WI, 74 lumbosacral spinal nerve roots from 31 patients showed compression changes. DTI showed thinning and distortion in 36 lumbosacral spinal nerve roots（49%） and abruption in 17 lumbosacral spinal nerve roots（23%）. Moreover, fractional anisotropy values were reduced in the lumbosacral spinal nerve roots of patients with lumbosacral stenosis. These findings suggest that DTI can objectively and quantitatively evaluate the severity of lumbosacral spinal nerve root compression.

关键词： nerve regeneration magnetic resonance imaging diffusion tensor imaging lumbosacralarea degeneration nerve root fractional anisotropy neural regeneration

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Single-cell multi-omics sequencing and its applications in studying the nervous system

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Biophysics Reports 2022年第3期8卷 136-149页

作者： Chaoyang Wang Xiaoying Fan Bioland Laboratory (guangzhou Regenerative Medicine and Health Guangdong Laboratory) the fifth affiliated hospital of guangzhou medical university

Single-cell sequencing has become one of the most powerful and popular techniques in dissecting molecular heterogeneity and modeling the cellular architecture of a biological system. During the past twenty years, the throughput of single-cell sequencing has increased from hundreds of cells to over tens of thousands of cells in parallel. Moreover, this technology has been developed from sequencing transcriptome to measure different omics such as DNA methylome, chromatin accessibility, and so ***, multi-omics which can analyze different omics in the same cell is rapidly advancing. This work advances the study of many biosystems, including the nervous system. Here, we review current single-cell multi-omics sequencing techniques and describe how they improve our understanding of the nervous system. Finally, we discuss the open scientific questions in neural research that may be answered through further improvement of single-cell multi-omics sequencing technology.

关键词： Single-cell sequencing Multi-omics Cell heterogeneity Nervous system

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